Cyclin D1 Expression in Breast Cancer Patients Receiving Adjuvant Tamoxifen-Based Therapy

• Published in: Clinical cancer research 2008-03, Vol.14 (6), p.1767-1774
• Main Authors: RUDAS, Margaretha, LEHNERT, Martina, KWASNY, Werner, GRILL, Renate, STIERER, Michael, GNANT, Michael F. X, FILIPITS, Martin, HUYNH, Anh, JAKESZ, Raimund, SINGER, Christian, LAX, Sigurd, SCHIPPINGER, Walter, DIETZE, Otto, GREIL, Richard, STIGLBAUER, Wolfgang
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Aminoglutethimide - administration & dosage; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Chemotherapy, Adjuvant; Cyclin D1 - metabolism; Cyclins; Cyclophosphamide - administration & dosage; Disease-Free Survival; Female; Fluorouracil - administration & dosage; Follow-Up Studies; Goserelin - administration & dosage; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Methotrexate - administration & dosage; Middle Aged; Pharmacology. Drug treatments; Prognosis; Receptors, Cytoplasmic and Nuclear - metabolism; Recurrence; Tamoxifen; Tamoxifen - administration & dosage; Tamoxifen - therapeutic use; Treatment Outcome; Tumors
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-07-4122

Purpose: The objective of our study was to determine the clinical relevance of cyclin D1 expression in hormone receptor–positive breast cancer patients who were treated with tamoxifen-based therapy. Experimental Design: We assessed expression of cyclin D1 in surgical specimens of breast carcinoma by means of immunohistochemistry. Patients had been enrolled in either Austrian Breast and Colorectal Cancer Study Group (ABCSG) Trial 05 or ABCSG Trial 06 and received tamoxifen as part of their adjuvant treatment. Overall survival and relapse-free survival were analyzed with Cox models adjusted for clinical and pathologic factors. Results: Cyclin D1 was expressed in 140 of 253 (55%) tumors of ABCSG Trial 05 and in 569 of 948 (60%) tumors of ABCSG Trial 06. Expression of cyclin D1 was associated with poor outcome in both cohorts. Overall survival was significantly shorter in patients with cyclin D1–positive tumors compared with patients with cyclin D1–negative tumors [adjusted hazard ratio (HR) for death (ABCSG Trial 05), 2.47; 95% confidence interval (95% CI), 1.08-5.63; P = 0.03; adjusted HR for death (ABCSG Trial 06), 1.78; 95% CI, 1.36-2.34; P < 0.0001]. Relapse-free survival was also shorter in patients with cyclin D1–positive tumors than in patients with cyclin D1–negative tumors [adjusted HR for relapse (ABCSG Trial 05), 2.73; 95% CI, 1.50-4.96; P = 0.001; adjusted HR for relapse (ABCSG Trial 06), 1.52; 95% CI, 1.14-2.04; P = 0.005]. Conclusion: Cyclin D1 expression is an independent poor prognostic factor in women with early-stage, hormone receptor–positive breast cancer who received adjuvant tamoxifen-based therapy.